Context Endothelial dysfunction is associated with cardiovascular risk, which in men has been linked with a paucity of bone marrow-derived endothelial progenitor cells (EPCs).[unreadable] [unreadable] Objective Our purpose was to determine predictors of endothelial function and cardiovascular risk for women with sedentary occupations and no regular exercise.[unreadable] [unreadable] Design, Setting and Participants We recruited 90 women (age range 22-63 years) who reported no routine exercise (71% overweight or obese) with no history of cardiovascular disease: 43 had 1 cardiovascular risk factor.[unreadable] [unreadable] Main Outcome Measures Endothelial function was determined by brachial artery flow-mediated dilation following 5 minutes of forearm ischemia. Peripheral blood mononuclear cells were evaluated for EPC colony formation after five days of culture in fibronectin-coated wells. Treadmill stress testing was performed with gas exchange analysis at peak exercise (peak VO2) to assess level of fitness.[unreadable] [unreadable] Results Brachial artery reactivity correlated positively with peak VO2 (r=0.4483, P<0.0001) and inversely with Framingham risk score (r=-0.3542, P=0.0007), age (r=-0.3420, P=0.0010), body-mass index (r=-0.3065, P=0.0035), C-reactive protein (r=-0.2220, P=0.0400) and marginally with follicle-stimulating hormone, total cholesterol and systolic blood pressure. EPC colonies were not associated with brachial artery flow-mediated dilation (r=0.0025, P=0.9810) or with Framingham risk score (r=-0.0144, P=0.8940), even when data were stratified by menopausal status and absence of therapies that might effect either measurement. By multiple linear regression analysis with stepwise modeling, peak VO2 (P=0.0003) remained as the best independent predictor of brachial artery reactivity. Peak VO2 was inversely associated with risk factor prevalence and predictive of Framingham risk score (r=-4455, P<0.0001), especially for obese women (r=-0.5414, P=0.0003).[unreadable] [unreadable] Conclusions Endothelial function is significantly associated with cardiovascular risk in sedentary women; EPCs are associated with neither. Instead, level of fitness is the dominant predictor of endothelial function and cardiovascular risk, even in overweight and obese women.